Many disease processes involve the complex immune system in various ways. The immune system is largely controlled by lymphocytes which are functionally diverse though morphologically uniform. This morphological uniformity hinders our effort in separating the complex immune system into simpler functional subunits which are easier to study. Hence clear identification of the functional subunits among lymphocytes should greatly aid our understanding immune functions. Following the evidence accumlated from animal studies described in this proposal, I will identify a human B lymphocyte subset producing IgG2 - an immunoglobulin class important for combating infection. To achieve this, my work is divided into 4 sections: A) DEVELOPMENT OF ANALYTICAL METHODS B) DEMONSTRATION OF FUNCTIONAL SUBSETS OF B LYMPHOCYTES C) ASSOCIATION OF THE FUNCTIONAL SUBSETS WITH KNOWN PHENOTYPIC MARKERS D) STUDY OF HYBRIDOMA ANTIBODIES RECOGNIZING THE FUNCTIONAL SUBSET. Clear demonstration of B lymphocyte subsets through this multipronged approach will help us understand the complex immune system and its relationship to medical problems. To a physician working in a diagnostic clinical laboratory, these new insights mean a possibility for new diagnostic and therapeutic approaches to many diseases including immunodeficiency diseases, infections, autoimmunity and malignancies such as leukemia. Indeed in a prior work, basic research into the immune response to group A carbohydrate antigen enabled us to improve the procedures for diagnosing group A streptococcal infection (J. Clin. Microbiol. 12:506, 1980).